Understanding How Clinicians Personalize Fluid and Vasopressor Decisions in Early Sepsis Management

This survey study assesses factors associated with personalizing decision-making regarding fluid and vasopressor administration among patients with sepsis.

Legend: Clinical factors that were randomized in cases 1-6.Fluid volume and MAP appeared in all cases 1-6.All other factors appeared only in pairs of cases, as designated in the Case column.⊥ Factor levels indicate the number of possible factors that were randomized.*Text that participants were randomly assigned to see within the cases.In the full survey (Appendix B), this is the text that would appear in the blue brackets.For example, {MAP} would be randomly assigned to populate with any of the listed MAPs in this column.• Upper arm, above Antecubital Fossa Legend: Clinical factors that were randomized in cases 7-10.All factors appeared in all cases.For all cases, the presented scenario was a patient with norepinephrine running through an 18 Gauge peripheral IV. ⊥ Factor levels indicate the number of possible factors that were randomized.*Text that participants were randomly assigned to see within the cases.In the full survey (Appendix B), this is the text that would appear in the blue brackets.For example, {dose} would be randomly assigned to populate with any of the listed doses in this column.
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Start of Block: Instructions
Q2 Section 1: Cases 1-6 You will be shown 6 short clinical cases and asked how you would manage these example patients who are presenting to your Intensive Care Unit with sepsis and hypotension.This survey is meant to assess provider practices; it is not meant to be a test of knowledge.
Please choose the answer that most reflects what you would do in your clinical practice in each scenario based on the information provided.Q36 Section 3: General Practice Please answer the following 4 questions to best describe your general (average) practice for managing new patients presenting with sepsis and hypotension.We know that there are many factors that influence your management of individual patients.This section is meant to provide an overview of your general practice.
Q37 The amount of IV fluid I give within the first 6 hours of a patient's presentation is usually:  We performed separate multivariable, multilevel logistic regression models to assess the association between the randomized clinical factors and respondent recommendations for 1) additional fluids and 2) vasopressors.We did this using both overall regressions (all cases 1-6) and regressions for each case pair, as outlined here: a. Overall regressions were performed pooling the results for cases 1-6.The goal of these regressions was to assess the overall association of fluid volume received and MAP with fluid/vasopressor recommendations.Fluid volume and MAP were randomized in all 6 cases.Factors were randomized individually for each case, so respondents could have theoretically seen the same fluid volume or MAP for all 6 cases.In these regressions, clinical factors from all cases were used as co-variates (fluid volume received, MAP, volume status exam, past medical history, oxygen requirement, respiratory rate, lactate trend, AKI).However, because clinical factors besides fluid volume and MAP were not randomized in all cases (e.g., oxygen requirement was randomized in cases 3 &4 but fixed as room air for cases 1, 2, 5, 6), the individual effects of these factors were not reported in the overall models.
Case number was also included as a co-variate to capture the impact of differences between case stems.Results are presented in e-Table 1 and e-Figure 4. b.Separate regressions were then performed for each case pair (cases 1 and 2, cases 3 and 4, cases 5 and 6).The goal of these regressions was to assess the association of the randomized factors within each case pair with respondent recommendations in those cases.The factors randomized in the case pair were included as co-variates in each regression (e.g., in cases 1 and 2, co-variates were: fluid volume received, MAP, volume status exam, past medical history).Factors were randomized individually for each case, so respondents could have theoretically seen the same value, e.g., dry volume exam, for both cases in the pair.Case number was also included as a covariate to capture the impact of differences between case stems.Results are presented in Figure 2 and e-Table 2. B. Peripheral vasopressor initiation: Among respondents who recommended vasopressors, we performed multivariable logistic regression models to determine the association of randomized factors with the decision to start vasopressors peripherally (vs via central access).Given each case included a different combination of baseline access (i.e., PIV, pre-existing CVC, Port, or PICC) and randomized factors, separate regressions were performed for each case.Given regression models were run individually for each case and each respondent answered each case once, multilevel modeling was not used.We did not perform a regression for case 2 given this case presented a patient with a pre-existing, new CVC which is the traditional gold standard route for vasopressor administration.
Results are presented in e-Table 6.

C. Case difficulty:
We performed a multivariable, multilevel logistic regression model to assess the association between fluid volume received, MAP, and case number with reported case difficulty.A case was defined as difficult if the respondent answered "somewhat difficult" or "very difficult" on the 5-point Likert scale.Results are presented in e-Table 4.
Cases 7-10 For cases 7-10, an overall multivariable, multilevel logistic regression model was performed to assess the association between randomized factors and the recommendation to place a central line.All randomized factors were included as covariates (vasopressor dose, dose trend, duration, and PIV location).Case number was also included as a co-variate to capture the impact of differences between case stems.Factors were randomized individually for each case, so respondents could have theoretically seen the same values for all 4 cases.Results are presented in Figure 3 and e-Table 7.
© with recommendations for fluids and vasopressors in cases 1-6.Odds ratios and adjusted proportion of respondents were determined using separate multivariable, multilevel logistic regression models for 1) the recommendation to prescribe fluid and 2) the recommendation to initiate vasopressors.Multilevel models were performed to allow clustering by participant ID, which was treated as a random effect.Fluid volume and MAP were randomized across all cases 1-6 and their overall effects are reported here.The other clinical factors included in cases 1-6 (volume status exam, medical history, oxygen requirement, respiratory rate, lactate trend, and acute kidney injury) were randomized in 2 out of 6 cases but kept constant in the other cases (e.g., oxygen requirement was randomized in cases 3 and 4 but kept constant at room air in cases 1, 2, 5, 6).These clinical factors were included as co-variates in these regressions, but given they were not randomized in each case, their overall effects are not reported.Effects of all randomized clinical factors are reported in separate case-paired regressions (in e-Table 2 and Figure 2).N=3,129 completed vignettes *Adjusted proportion of respondents (also known as average predicted probabilities) were calculated using predictive margins after fitting each regression model.These predicted probabilities represent the proportion of respondents (as a percentage) recommending fluids or vasopressors based on the listed factors, after adjusting for all other factors in the model.4a Legend: Association of randomized clinical factors with participant recommendation for fluids and vasopressors in cases 1 and 2. Odds ratios and adjusted proportion of respondents were determined using separate multivariable, multilevel logistic regression models for 1) the recommendation to prescribe fluid and 2) the recommendation to initiate vasopressors.Multilevel models were performed to allow clustering by participant ID, which was treated as a random effect.N=1,043 completed vignettes eTable 2c.72.2 (68.9, 75.4) e-Table 4c Legend: Association of randomized clinical factors with participant recommendation for fluids and vasopressors in cases 5 and 6.Odds ratios and adjusted proportion of respondents were determined using separate multivariable, multilevel logistic regression models for 1) the recommendation to prescribe fluid and 2) the recommendation to initiate vasopressors.Multilevel models were performed to allow clustering by participant ID, which was treated as a random effect.N=1,041 completed vignettes.† Corresponds to Figure 1c.*Adjusted proportion of respondents (also known as average predicted probabilities) were calculated using predictive margins after fitting each regression model.These predicted probabilities represent the proportion of respondents (as a percentage) recommending fluids or vasopressors based on the listed factors, after adjusting for all other factors in the model.Comparison of participant characteristics to characteristics of SCCM members who were sent the electronic survey.SCCM member demographics were provided by SCCM.N=550 providers completed the first clinical vignette of this survey and were considered study participants.Information was missing or not reported for gender (N=97), clinical role (N=80), region of practice (N=80).The survey was sent to 11,203 SCCM members (US-based critical care providers).Clinical role was available for all SCCM members; information was missing for gender (N=5,681) and region of practice (N=46).*p-values were determined using Chi-Squared tests of difference.Comparisons were made after excluding missing information.2 Legend: Association of fluid volume, MAP and case with perceived case difficulty assessed using a multivariable, multilevel logistic regression for difficult decision.In the multilevel model, responses were clustered by participant.N=3,097 completed vignettes † Participants were asked to rate the difficulty of each on a five-point Likert scale.A difficult decision was defined as a response of "very difficult" and "somewhat difficult."*Adjusted proportion of respondents (also known as average predicted probabilities) were calculated using predictive margins after fitting the regression model.These predicted probabilities represent the proportion of respondents (as a percentage) reporting a difficult decision based on the listed factors, after adjusting for all other factors in the model.**Case 2 was selected as the reference case because the patient presented in case 2 had a temporary central venous catheter, the gold standard route for vasopressor administration.Patients presented in other cases had only peripheral IVs (cases 1,3,5), a pre-existing Port (case 4), or a pre-existing peripherally-inserted central catheter (case 6).The other clinical factors included in cases 1-6 (volume status exam, medical history, oxygen requirement, respiratory rate, lactate trend, and acute kidney injury) were randomized in 2 out of 6 cases but kept constant in the other cases (e.g., oxygen requirement was randomized in cases 3 and 4 but kept constant at room air in cases 1, 2, 5, 6).These clinical factors were included as co-variates in these regressions, but given they were not randomized in each case, their overall effects are not reported.Effects of all randomized clinical factors are reported in separate case-paired regressions (in e- Here we present themes identified from review of free-text "other" responses (N=63 participants).

Definitions
a For example, central access needed for other medications, medication incompatibility, lab draws, or CVP/SvO2 monitoring; inability to attain peripheral intravenous access.
b For example, "business of the unit"; time of day; physician availability; availability of a team capable of placing a peripherally-inserted central catheter (PICC); availability of subspeciality care.

oQ22
X is a 78 year old man with diabetes, coronary artery disease s/p RCA stent in 2012, and {Past Medical History} who was brought to the ED by his daughter after she found him confused at home.He was febrile and hypotensive on arrival.The ED team started broad spectrum antibiotics for suspected sepsis of unclear source.On exam, patient is A&Ox1 with {volume exam}.SpO2 94% on room air.Labs are pending.IV fluids received: {fluid volume} Current BP: {MAP} Access: 2 peripheral IVs What would you do next to manage this patient's low blood pressure?o Give additional IV fluids (1) o Give additional IV fluids and initiate vasopressors (2) o Initiate vasopressors without giving additional IV fluids (3) o No additional intervention; monitor and re-assess (4) o Peripheral IV (1) o Peripheral IV but plan to place a central line (2) o Central line (3) Q124 How difficult was it to decide on the next step in management in this case?o Very difficult (1) o Somewhat difficult (2) o Neutral (3) o Somewhat easy (4) o Very easy (5) Q5 (OPTIONAL) Do you have any other comments on this case?________________________________________________________________ o Give additional IV fluids (1) o Give additional IV fluids and initiate vasopressors (2) o Initiate vasopressors without giving additional IV fluids (3) o No additional intervention; monitor and re-assess (4) o Very difficult (1) o Somewhat difficult (2) o Neutral (3) o Somewhat easy (4) o Very easy (5) Q7 (OPTIONAL) Do you have any other comments on this case?________________________________________________________________ End of Block: Initial cases 2 Start of Block: Initial cases 3Q8 Mr. M is a 66 year old man with a history of non-small cell lung cancer s/p chemo/radiation therapy in 2020 who presents with 2 days of fever and cough.Chest x-ray shows a left lower lobe pneumonia.The ED team has started appropriate antibiotics.On your evaluation, SpO2 is 94% on {oxygen support} and {respiratory rate}.Patient is A&Ox3, mucus membranes are moist, no lower extremity edema.Labs are pending.IV fluids received: {fluid volume} Current BP: {MAP} Access: 2 peripheral IVs What would you do next to manage this patient's low blood pressure?o Give additional IV fluids (1) o Give additional IV fluids and initiate vasopressors (2) o Initiate vasopressors without giving additional IV fluids (3) o No additional intervention; monitor and re-assess (4) Peripheral IV (1) o Peripheral IV but plan to place a central line (2) o Central line (3) o Very difficult (1) o Somewhat difficult (2) o Neutral (3) o Somewhat easy (4) o Very easy (5) Q10 (OPTIONAL) Do you have any other comments on this case?________________________________________________________________ o Give additional IV fluids (1) o Give additional IV fluids and initiate vasopressors (2) o Initiate vasopressors without giving additional IV fluids (3) o No additional intervention; monitor and re-assess (4) ES et al.JAMA Network Open.Q12 How would you start vasopressors?o Existing PORT (4) o Peripheral IV (1) o Peripheral IV but plan to place a new central line (2) o New central line (3) Q127 How difficult was it to decide on the next step in management in this case?o Very difficult (1) o Somewhat difficult (2) o Neutral (3) o Somewhat easy (4) o Very easy (5) Q13 (OPTIONAL) Do you have any other comments on this case?________________________________________________________________ End of Block: Initial cases 4 Start of Block: Initial cases 5 Q14 Ms.A is a 56 year old woman with obesity, obstructing renal stones s/p left nephrostomy tube, and recurrent urinary tract infections who presents to the ED with suspected urosepsis in the setting of 3 days of urinary frequency, left flank pain, and fevers.There is worsened left hydronephrosis on CT imaging.The ED team has started appropriate antibiotics based on prior culture data.They are also contacting Interventional Radiology and Urology about possible intervention.On exam, patient is A&Ox3 and uncomfortable with left flank tenderness.Mucus membranes are moist, no lower extremity edema.SpO2 96% on room air.Labs are notable for {lactate trend}.{AKI} IV fluids received: {fluid volume} Current BP: {MAP} Access: 2 peripheral IVs What would you do next to manage this patient's low blood pressure?o Give additional IV fluids (1) o Give additional IV fluids and initiate vasopressors (2) o Initiate vasopressors without giving additional IV fluids (3) o No additional intervention; monitor and re-assess (4) ES et al.JAMA Network Open.Q15 How would you start vasopressors?o Peripheral IV (1) o Peripheral IV but plan to place a central line (2) o Central line (3) Q128 How difficult was it to decide on the next step in management in this case?o Very difficult (1) o Somewhat difficult (2) o Neutral (3) o Somewhat easy (4) o Very easy (5) Q16 (OPTIONAL) Do you have any other comments on this case?________________________________________________________________ End of Block: Initial cases 5 Start of Block: Initial cases 6 Q17 Ms. F is a 59 year old woman with obesity and a recent admission for acute cholecystitis s/p percutaneous cholecystostomy tube.She presents to the ED after dislodgement of the cholecystectomy tube with RUQ pain and fevers.The ED team is concerned about recurrent cholecystitis.They have started antibiotics and are consulting Interventional Radiology and Surgery for possible intervention.On exam, patient is A&Ox3 with RUQ tenderness.Mucus membranes are moist, no lower extremity edema.SpO2 95% on room air.Labs are notable for {lactate trend}.{AKI} IV fluids received: {fluid volume} Current BP: {MAP} Access: Dual-lumen upper extremity PICC (peripherally inserted central catheter) still in place from patient's recent admission.What would you do next to manage this patient's low blood pressure?o Give additional IV fluids (1) o Give additional IV fluids and initiate vasopressors (2) o Initiate vasopressors without giving additional IV fluids (3) o No additional intervention; monitor and re-assess (4) ES et al.JAMA Network Open.Q18 How would you start vasopressors?o Existing PICC (4) o Peripheral IV (1) o Peripheral IV but plan to place a new central line (2) o New central line (3) Q129 How difficult was it to decide on the next step in management in this case?o Very difficult (1) o Somewhat difficult (2) o Neutral (3) o Somewhat easy (4) o Very easy (5) Q19 (OPTIONAL) Do you have any other comments on this case?10, you are receiving hand-off about the following patients who were recently admitted to the Intensive Care Unit for septic shock requiring vasopressors.These patients are currently receiving norepinephrine through an 18 gauge peripheral IV.Assume each patient has been adequately resuscitated and has adequate IV access for lab draws and the other medications they are receiving, including antibiotics and fluids.infuse norepinephrine for this patient during your shift?(Choose one) o Continue using this peripheral IV (1) o Continue using this peripheral IV in the short term, but reassess need for a central line in the next few hours (2) o Place a central line for norepinephrine now (3) o Obtain alternative access for norepinephrine (other than a central line: e.g.What alternative access would you place to administer norepinephrine?o New peripheral IV (e.g., an IV that is larger, in a new location, or ultrasound-guided) (1) o Midline catheter (2) o PICC (peripherally-inserted central catheter) (3) o Other (4) __________________________________________________ Q23 (OPTIONAL) Do you have any other comments on this case?infuse norepinephrine for this patient during your shift?(Choose one) o Continue using this peripheral IV (1) o Continue using this peripheral IV in the short term, but reassess need for a central line in the next few hours (2) o Place a central line for norepinephrine now (3) o Obtain alternative access for norepinephrine (other than a central line: e.g., a new peripheral IV, PICC) (4) Display This Question: If Q24 = 4 Q25 What alternative access would you place to infuse norepinephrine?o New peripheral IV (e.g., an IV that is larger, in a new location, or ultrasound-guided) (1) o Midline catheter (2) o PICC (peripherally-inserted central catheter) (3) o Other (4) __________________________________________________ Q26 (OPTIONAL) Do you have any other comments on this case?________________________________________________________________ End of Block: Peripheral VP Case 8 © 2024 Munroe ES et al.JAMA Network Open.infuse norepinephrine for this patient during your shift?(Choose one) o Continue using this peripheral IV (1) o Continue using this peripheral IV in the short term, but reassess need for a central line in the next few hours (2) o Place a central line for norepinephrine now (3) o Obtain alternative access for norepinephrine (other than a central line: e.g., a new peripheral IV, PICC) (4) Display This Question: If Q27 = 4 Q28 What alternative access would you place to infuse norepinephrine?o New peripheral IV (e.g., an IV that is larger, in a new location, or ultrasound-guided) (1) o Midline catheter (2) o PICC (peripherally-inserted central catheter) (3) o Other (4) __________________________________________________ Q29 (OPTIONAL) Do you have any other comments on this case? in the {location} How would you infuse norepinephrine for this patient during your shift?(Choose one) o Continue using this peripheral IV (1) o Continue using this peripheral IV in the short term, but reassess need for a central line in the next few hours (2) o Place a central line for norepinephrine now (3) o Obtain alternative access for norepinephrine (other than a central line: e.g., a new peripheral IV, PICC) (4) Display This Question: If Q30 = 4 Q31 What alternative access would you place to infuse norepinephrine?oNew peripheral IV (e.g., an IV that is larger, in a new location, or ultrasound-guided) (1) a patient's MAP is below my target, I usually start vasopressors o Before giving fluid (1) o While giving fluid (2) o After giving fluid (3) o Never, I don't use vasopressors (4)

eFigure 2 .
Self-Reported Usual Practices For Managing Patients With New Sepsis-Induced Hypotension e-Figure 2 Legend.Respondents were asked to report their usual (average) practices for managing patients with new sepsis-induced hypotension.A. Amount of IV fluid given within the first 6 hours of patient presentation, in liters.B. Mean Arterial Pressure (MAP) goal, in mmHg.C. Timing of vasopressor initiation for patients with persistent hypotension.D. Route of vasopressor initiation.eFigure 3. Range of Respondent Answers Across Cases eFigure 3 Legend: This figure depicts the range respondent answers across cases.Making the same choice in none (0) or all cases may reflect that a respondent has a set practice that they were not changing based on factors in the case.In contrast, choosing a response in only some of the cases (e.g., 3/6 cases) may indicate that the respondent was personalizing care-or changing their response-based on the factors presented in the cases.

eFigure 4 .
Range of Respondent Answers Across Cases Where Participants Saw the Same Fluid Volume Already Received eFigure 4 Legend: This figure depicts the variation in respondent recommendations for fluids and vasopressors across cases where respondents saw the same fluid volume volume already received.Respondents were included if they saw the same fluid volume already received in ≥ 2 cases (e.g., saw 2 or more cases where the fluid volume already received was 1L, in panel A).Red and blue represent the percent of respondents who always made the same recommendations in cases with the same fluid volume already received, either never (red) or always (blue) making a recommendation.Yellow represents the number of respondents who made different recommendations across cases where they saw the same fluid volume already received (e.g., started fluids in only some of the cases they saw with the same fluid volume).This yellow portion reflects the percent of respondents whose decisions appeared to depend on other factors in the case.

Definitions:
MAP= Mean Arterial Pressure, CI= Confidence Interval eFigure 5. Overall Association of Fluid Volume and MAP With Recommendations for Fluids and Vasopressors, Cases 1-6 eFigure 5 Legend: Adjusted proportion of respondents recommending fluids or vasopressors by fluid volume and MAP in cases 1-6.Fluid volume and MAP were randomized across all cases 1-6 and their overall effects are reported here.

End of Block: Follow-up questions Start of Block: General Practice Pattern
Q34 (OPTIONAL) Do you have any comments about the cases presented?________________________________________________________________ Q35 In your practice, for patients whose only indication for central access is vasopressor infusion, what factor most influences your decision to place a central line?

End of Block: Background Start of Block: Wrap-up Q53
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________________________________________________________________End of Block: General Practice Pattern Start of Block: Background Q42 Section 3: Background These final few questions ask for anonymous information about you and your clinical practice setting.You may choose to skip any questions that you are not comfortable answering.Q43 What is your clinical role?o Physician (1) o Advanced Practice Provider (NP or PA) (2) o Other (3) __________________________________________________ Q45 To which gender identity do you most identify?
Association of Fluid Volume and MAP With Recommendations for Fluids and Vasopressors, Cases 1-6 2024 Munroe ES et al.JAMA Network Open.eTable 1.

. Association of Randomized Clinical Factors WIth Recommendations for Fluids and Vasopressors eTable 2a.
Association of randomized clinical factors with recommendations for fluids and vasopressors, Cases 1 and 2 † Association of randomized clinical factors with recommendations for fluids and vasopressors, Cases 5 and 6 †

:
OR= odds ratio, Ref= reference value; MAP= mean arterial pressure, Lactate decreasing= initial lactate 4.1 mmol/L decreased to 2.7 mmol/L with fluids, Lactate repeat pending= initial lactate 4.1 mmol/L with repeat pending, Lactate increasing= initial lactate 4.1 mmol/L increased to 5.4mmol/L despite fluids; PICC=peripherally-inserted central catheter eTable 3. Characteristics of Survey Participants Compared to Society of Critical Care Medicine (SCCM) Providers Who Received the Survey

eTable 4 .
Association of Fluid Volume, MAP, and Case With Perceived Case Difficulty, Cases 1-6

Adequacy of fluid resuscitation 3 Risks of Central Venous Catheter Placement 2 Urgency of Vasopressor Initiation 2 Prior Experience with Peripheral Vasopressor Complications 1
Association of randomized clinical factors with peripheral vasopressor initiation, when baseline vascular access was a PIV † , patients only had peripheral IVs as their baseline vascular access.Case 1: N= 406, Case 3: N=374, Case 5: N= 347.Participants only answered this question if they recommended vasopressors in the case.*Adjustedproportion of respondents (also known as average predicted probabilities) were calculated using predictive margins after fitting each regression model.These predicted probabilities represent the proportion of respondents (as a percentage) starting vasopressors peripherally (PIV only or PIV as a bridge to central access) based on the listed factors, after adjusting for all other factors in the model.Definitions: PIV= peripheral IV, Ref= reference value; CI= confidence interval; MAP= mean arterial pressure; Dry= dry mucus membranes and decreased skin turgor, Euvolemic = moist mucus membranes and normal jugular venous pressure, Wet= elevated jugular venous pressure and bilateral 1+ pitting edema; COPD= Chronic Obstructive Pulmonary Disease, ESRD= end-stage renal disease, HD= hemodialysis-dependent, HFrEF= heart failure with reduced ejection fraction; NC= nasal cannula, Respiratory rate levels: 20 breaths per minute and no accessory muscle use; 30 breaths per minute and mild accessory muscle use,40 breaths per minute and notable accessory muscle use; Lactate decreasing= initial lactate 4.1 mmol/L decreased to 2.7 mmol/L with fluids, Lactate repeat pending= initial lactate4.1 mmol/L with repeat pending, Lactate increasing= initial lactate 4.1 mmol/L increased to 5.4mmol/L despite fluids; PICC=peripherally-inserted central catheter eTable 8. Identified Themes From a Free-Text Question Eliciting Factors That Contributed to Respondents' Decision to Place a Central Line in Patients on Peripheral Vasopressors, Cases 7-10Legend: This table displays the themes identified by reviewing responses.In free-text comments, N=33 respondents commented on additional information they would use to make decisions about central line placement in cases 7-10.These themes represent factors that participants reported using when making decisions about when to place central lines in patients on peripheral vasopressors.Identified Themes From a Free-Text Question About Most Important Factors Impacting Decision About Peripheral Vasopressor Use Lactate 1 Legend: Providers were asked "In your practice, for patients whose only indication for central access is vasopressor infusion, what factor most influences your decision to place a central line?' Answer options were: hospital policy, nursing preference, personal practice, and "other," with an associated free-text box.